典型文献
Atractylenolide-Ⅰ covalently binds to CYP11B2,selectively inhibits aldosterone synthesis,and improves hyperaldosteronism
文献摘要：
Hyperaldosteronism is a common disease that is closely related to endocrine hypertension and other cardiovascular diseases.Cytochrome P450 11B2(CYP11B2),an important enzyme in aldoste-rone(ALD)synthesis,is a promising target for the treatment of hyperaldosteronism.However,selective inhibitors targeting CYP11B2 are still lacking due to the high similarity with CYP11B1.In this study,atractylenolide-Ⅰ(AT-Ⅰ)was found to significantly reduce the production of ALD but had no effect on cortisol synthesis,which is catalyzed by CYP11B1.Chemical biology studies revealed that due to the presence of Ala320,AT-Ⅰ is selectively bound to the catalytic pocket of CYP11B2,and the C8/C9 double bond of AT-Ⅰ can be epoxidized,which then undergoes nucleophilic addition with the sulfhydryl group of Cys450 in CYP11B2.The covalent binding of AT-Ⅰ disrupts the interaction between heme and CYP11B2 and inactivates CYP11B2,leading to the suppression of ALD synthesis;AT-Ⅰ shows a significant thera-peutic effect for improving hyperaldosteronism.
文献关键词：
中图分类号：
作者姓名：
Wenjuan Liu;Zhenqiang Li;Simeng Chu;Xiaoyao Ma;Xiaoying Wang;Min Jiang;Gang Bai
作者机构：
State Key Laboratory of Medicinal Chemical Biology,College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research,Nankai University,Tianjin 300353,China;Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China
文献出处：
引用格式：
[1]Wenjuan Liu;Zhenqiang Li;Simeng Chu;Xiaoyao Ma;Xiaoying Wang;Min Jiang;Gang Bai-.Atractylenolide-Ⅰ covalently binds to CYP11B2,selectively inhibits aldosterone synthesis,and improves hyperaldosteronism)[J].药学学报（英文版）,2022(01):135-148
A类：
Atractylenolide,Hyperaldosteronism,11B2,aldoste,rone,atractylenolide,Ala320,epoxidized,Cys450
B类：
covalently,binds,CYP11B2,selectively,inhibits,aldosterone,synthesis,improves,hyperaldosteronism,common,that,closely,related,endocrine,hypertension,other,cardiovascular,diseases,Cytochrome,P450,important,enzyme,ALD,promising,treatment,However,inhibitors,targeting,are,still,lacking,due,high,similarity,CYP11B1,In,this,study,AT,was,found,significantly,reduce,production,but,had,effect,cortisol,which,catalyzed,by,Chemical,biology,studies,revealed,presence,bound,catalytic,pocket,C8,C9,double,bond,then,undergoes,nucleophilic,addition,sulfhydryl,group,binding,disrupts,interaction,between,heme,inactivates,leading,suppression,shows,thera,peutic,improving
AB值：
0.529932
相似文献
机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
